Impact of depressed state on attention and language processing during news broadcasts: EEG analysis and machine learning approach.

While information enriches daily life, it can also sometimes have a negative impact, depending on an individual's mental state. We recorded electroencephalogram (EEG) signals from depressed and non-depressed individuals classified based on the Beck Depression Inventory-II score while they listened to news to clarify differences in their attention to affective information and the impact of attentional bias on language processing. Results showed that depressed individuals are characterized by delayed attention to positive news and require a more increased load on language processing. The feasibility of detecting a depressed state using these EEG characteristics was evaluated by classifying individuals as depressed and non-depressed individuals. The area under the curve in the models trained by the EEG features used was 0.73. This result shows that individuals' mental states may be assessed based on EEG measured during daily activities like listening to news.

Prediction of Second Language Proficiency Based on Electroencephalographic Signals Measured While Listening to Natural Speech.

This study had two goals: to clarify the relationship between electroencephalographic (EEG) features estimated while non-native speakers listened to a second language (L2) and their proficiency in L2 determined by a conventional paper test and to provide a predictive model for L2 proficiency based on EEG features. We measured EEG signals from 205 native Japanese speakers, who varied widely in English proficiency while they listened to natural speech in English. Following the EEG measurement, they completed a conventional English listening test for Japanese speakers. We estimated multivariate temporal response functions separately for word class, speech rate, word position, and parts of speech. We found significant negative correlations between listening score and 17 EEG features, which included peak latency of early components (corresponding to N1 and P2) for both open and closed class words and peak latency and amplitude of a late component (corresponding to N400) for open class words. On the basis of the EEG features, we generated a predictive model for Japanese speakers' English listening proficiency. The correlation coefficient between the true and predicted listening scores was 0.51. Our results suggest that L2 or foreign language ability can be assessed using neural signatures measured while listening to natural speech, without the need of a conventional paper test.

Advantage of Handwriting Over Typing on Learning Words: Evidence From an N400 Event-Related Potential Index.

The growing implementation of digital education comes with an increased need to understand the impact of digital tools on learning. Previous behavioral studies have shown that handwriting on paper is more effective for learning than typing on a keyboard. However, the impact of writing with a digital pen on a tablet remains to be clarified. In the present study, we compared learning by handwriting with an ink pen on paper, handwriting with a digital pen on a tablet, and typing on a keyboard. Behavioral and electroencephalographic indices were measured immediately after learning with each writing tool. The moods of the subjects during the training were also assessed. The participants were divided according to their use of digital pen in their everyday lives, allowing us to take into account the effect of the familiarity with the digital pen on the learning process (familiar group vs. unfamiliar group). We performed an EEG experiment applying a repetition priming paradigm. In each trial, a learned foreign language word (prime word) and a mother tongue word (target word) were consecutively presented. The target word was either semantically identical to the prime word (repetitive condition) or different (non-repetitive condition). We assumed that a larger priming effect on N400 reflects larger learning progress. The familiar group showed a greater N400 priming effect for words learned with the digital or ink pen than those learned with the keyboard. The unfamiliar group showed the greater N400 priming effect for words learned with the ink pen compared with words learned by typing. In addition, positive mood during learning was significantly higher during handwriting than during typing, regardless of the groups. On the other hand, the behavioral indices were not influenced by the writing tool. These results suggest that the movements involved in handwriting allow a greater memorization of new words. The advantage of handwriting over typing might also be caused by a more positive mood during learning. Finally, our results show that handwriting with a digital pen and tablet can increase the ability to learn compared with keyboard typing once the individuals are accustomed to it.

Distinctive responses in anterior temporal lobe and ventrolateral prefrontal cortex during categorization of semantic information.

Semantic categorization is a fundamental ability in language as well as in interaction with the environment. However, it is unclear what cognitive and neural basis generates this flexible and context dependent categorization of semantic information. We performed behavioral and fMRI experiments with a semantic priming paradigm to clarify this. Participants conducted semantic decision tasks in which a prime word preceded target words, using names of animals (mammals, birds, or fish). We focused on the categorization of unique marine mammals, having characteristics of both mammals and fish. Behavioral experiments indicated that marine mammals were semantically closer to fish than terrestrial mammals, inconsistent with the category membership. The fMRI results showed that the left anterior temporal lobe was sensitive to the semantic distance between prime and target words rather than category membership, while the left ventrolateral prefrontal cortex was sensitive to the consistency of category membership of word pairs. We interpreted these results as evidence of existence of dual processes for semantic categorization. The combination of bottom-up processing based on semantic characteristics in the left anterior temporal lobe and top-down processing based on task and/or context specific information in the left ventrolateral prefrontal cortex is required for the flexible categorization of semantic information.

Enhancement of Facilitation Training for Aphasia by Transcranial Direct Current Stimulation.

We aimed to enhance the performance of naming and sentence production in chronic post-stroke aphasia by tablet-based language training combined with transcranial direct current stimulation (tDCS) conducted on non-consecutive days. We applied a deblocking method involved in stimulation-facilitation therapy to six participants with chronic aphasia who performed naming and sentence production tasks for impaired modalities, immediately after a spoken-word picture-matching task for an intact modality. The participants took part in two conditional sessions: a tDCS condition in which they performed a spoken word-picture matching task while we delivered an anodal tDCS over the left inferior frontal cortex; and a sham condition in which sham stimulation was delivered. We hypothesized that, compared with the sham stimulation, the application of anodal tDCS over the left inferior frontal cortex during the performance of tasks requiring access to semantic representations would enhance the deblocking effect, thereby improving the performances for subsequent naming and sentence production. Our results showed greater improvements 2 weeks after training with tDCS than those after training with sham stimulation. The accuracy rate of naming was significantly higher in the tDCS condition than in the sham condition, regardless of whether the words were trained or not. Also, we found a significant improvement in the production of related words and sentences for the untrained words in the tDCS condition, compared with that found pre-training, while in the sham condition we found no significant improvement compared with that found pre-training. These results support our hypothesis and suggest the effectiveness of the use of tDCS during language training on non-consecutive days.

Differences in Brain Activity After Learning With the Use of a Digital Pen vs. an Ink Pen-An Electroencephalography Study.

The purpose of this study is to clarify whether there is a learning effect on brain activity after writing with an ink pen vs. a digital pen. Previous studies have reported the superiority of handwriting to typing in terms of learning performance, but differences between the use of an ink pen vs. a digital pen remain unclear. In the present study, the participants learned to read difficult words by writing with an ink pen vs. a digital pen. After the learning period, electroencephalography (EEG) signals were measured, while the participants underwent a repetition priming paradigm with the use of the learned words. The repetition priming effect of the N400 event-related potential (ERP) was quantified as an index of the learning effect and the effects between pen types were compared. The groups were also subdivided according to whether a digital pen is frequently used (familiar vs. unfamiliar group). The number of writing repetitions for each word within 10 min during the learning activity and the post-learning test scores were not affected by the pen-type or familiarity with a digital pen. However, the repetition priming effect of the N400 was greater for words written with a digital pen in the learning session, as compared with an ink pen, in the familiar group, but not the unfamiliar group. These results suggest that for those familiar with its use, writing with a digital pen may improve learning relative to the use of an ink pen.

Temporospatial identification of language-related cortical function by a combination of transcranial magnetic stimulation and magnetoencephalography.

INTRODUCTION: Identification of language-related cortical functions can be carried out noninvasively by transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG), which allow for lesion-based interrogation and global temporospatial investigation of cortices, respectively. Combining these two modalities can improve the accuracy of the identification, but the relationships between them remain unclear. We compared TMS and MEG responses during the same language task to elucidate their temporospatial relationships and used the results to develop a novel method to identify language-related cortical functions. METHODS: Twelve healthy right-handed volunteers performed a picture-naming task during TMS and MEG. TMS was applied on the right or left inferior frontal gyrus (IFG) at five time points, and the reaction times (RTs) for naming the pictures were measured. The temporospatial oscillatory changes measured by MEG during the same task were then compared with the TMS results. RESULTS: Transcranial magnetic stimulation of the left IFG significantly lengthened RTs at 300 and 375 msec after picture presentation, whereas TMS of the right IFG did not change RTs significantly. Interestingly, the stimulus time point at which RTs increased significantly for each individual was correlated with when the low gamma event-related desynchronizations (ERDs) peaked in the left IFG. Moreover, combining the results of TMS and MEG improved the detection rate for identifying the laterality of language function. CONCLUSIONS: These results suggest that the low gamma ERDs measured by MEG strongly relate to the language function of picture naming in the left IFG. Finally, we propose a novel method to identify language-related cortical functions by combining TMS and MEG.

Selective increase of intention-based economic decisions by noninvasive brain stimulation to the dorsolateral prefrontal cortex.

The intention behind another's action and the impact of the outcome are major determinants of human economic behavior. It is poorly understood, however, whether the two systems share a core neural computation. Here, we investigated whether the two systems are causally dissociable in the brain by integrating computational modeling, functional magnetic resonance imaging, and transcranial direct current stimulation experiments in a newly developed trust game task. We show not only that right dorsolateral prefrontal cortex (DLPFC) activity is correlated with intention-based economic decisions and that ventral striatum and amygdala activity are correlated with outcome-based decisions, but also that stimulation to the DLPFC selectively enhances intention-based decisions. These findings suggest that the right DLPFC is involved in the implementation of intention-based decisions in the processing of cooperative decisions. This causal dissociation of cortical and subcortical backgrounds may indicate evolutionary and developmental differences in the two decision systems.

New human-specific brain landmark: the depth asymmetry of superior temporal sulcus.

Identifying potentially unique features of the human cerebral cortex is a first step to understanding how evolution has shaped the brain in our species. By analyzing MR images obtained from 177 humans and 73 chimpanzees, we observed a human-specific asymmetry in the superior temporal sulcus at the heart of the communication regions and which we have named the "superior temporal asymmetrical pit" (STAP). This 45-mm-long segment ventral to Heschl's gyrus is deeper in the right hemisphere than in the left in 95% of typical human subjects, from infanthood till adulthood, and is present, irrespective of handedness, language lateralization, and sex although it is greater in males than in females. The STAP also is seen in several groups of atypical subjects including persons with situs inversus, autistic spectrum disorder, Turner syndrome, and corpus callosum agenesis. It is explained in part by the larger number of sulcal interruptions in the left than in the right hemisphere. Its early presence in the infants of this study as well as in fetuses and premature infants suggests a strong genetic influence. Because this asymmetry is barely visible in chimpanzees, we recommend the STAP region during midgestation as an important phenotype to investigate asymmetrical variations of gene expression among the primate lineage. This genetic target may provide important insights regarding the evolution of the crucial cognitive abilities sustained by this sulcus in our species, namely communication and social cognition.

Facilitated lexical ambiguity processing by transcranial direct current stimulation over the left inferior frontal cortex.

Previous studies suggest that the left inferior frontal cortex is involved in the resolution of lexical ambiguities for language comprehension. In this study, we hypothesized that processing of lexical ambiguities is improved when the excitability of the left inferior frontal cortex is enhanced. To test the hypothesis, we conducted an experiment with transcranial direct current stimulation (tDCS). We investigated the effect of anodal tDCS over the left inferior frontal cortex on behavioral indexes for semantic judgment on lexically ambiguous and unambiguous words within a context. Supporting the hypothesis, the RT was shorter in the anodal tDCS session than in the sham session for ambiguous words. The results suggest that controlled semantic retrieval and contextual selection were facilitated by anodal tDCS over the left inferior frontal cortex.

Accuracy of estimating strengths of dipole moments from a small number of magnetoencephalographic trial data.

The conventional analysis estimates both the locations and strengths of neural source activations from event-related magnetoencephalography data that are averaged across about a hundred trials. In the present report, we propose a new method based on a minimum modified-l 1-norm to obtain the dependence of strengths on the presented stimuli from a limited number of trial data. It estimates the strengths from 10-trial average data and the locations from 100-trial average data. The method can be applied to neural activations whose strengths, but not locations, depend on the presented stimuli. For instance, it can be used in experiments in which the activation in the anterior temporal area (aT) is measured by varying semantic relatedness between stimuli in linguistic experiments. We conducted a realistic simulation, following previous experiments on lexico-semantic processing, in which five neural sources were simultaneously activated. The results showed that when the signal-to-noise ratio was one for non-averaged data, the proposed method had standard deviations of 13 % for the normalized strengths in the aT. It is inferred on the basis of the general linear model in which the strength has a linear dependence on the stimulus parameters that the proposed method can detect the dependence at a significance level of 1 % if the peak-to-peak change in normalized strength is more than 49 %. It is smaller than 66 % for the conventional method, which estimated locations and strengths from 10-trial data for each point. Thus, the proposed method can plot an activation-strength versus stimulus-parameter curve with better sensitivity.

Language comprehension dependent on emotional context: a magnetoencephalography study.

In communication, language can be interpreted differently depending upon the emotional context. To clarify the effect of emotional context on language processing, we performed experiments using a cross-modal priming paradigm with an auditorily presented prime and a visually presented target. The primes were the names of people that were spoken with a happy, sad, or neutral intonation; the targets were interrogative one-word sentences with emotionally neutral content. Using magnetoencephalography, we measured neural activities during silent reading of the targets presented in a happy, sad, or neutral context. We identified two conditional differences: the happy and sad conditions produced less activity than the neutral condition in the right posterior inferior and middle frontal cortices in the latency window from 300 to 400 ms; the happy and neutral conditions produced greater activity than the sad condition in the left posterior inferior frontal cortex in the latency window from 400 to 500 ms. These results suggest that the use of emotional context stored in the right frontal cortex starts at ∼300 ms, that integration of linguistic information with emotional context starts at ∼400 ms in the left frontal cortex, and that language comprehension dependent on emotional context is achieved by ∼500 ms.

Masked immediate-repetition-priming effect on the early lexical process in the bilateral anterior temporal areas assessed by neuromagnetic responses.

A masked priming paradigm has been used to measure unconscious and automatic context effects on the processing of words. However, its spatiotemporal neural basis has not yet been clarified. To test the hypothesis that masked repetition priming causes enhancement of neural activation, we conducted a magnetoencephalography experiment in which a prime was visually presented for a short duration (50 ms), preceded by a mask pattern, and followed by a target word that was represented by a Japanese katakana syllabogram. The prime, which was identical to the target, was represented by another hiragana syllabogram in the "Repeated" condition, whereas it was a string of unreadable pseudocharacters in the "Unrepeated" condition. Subjects executed a categorical decision task on the target. Activation was significantly larger for the Repeated condition than for the Unrepeated condition at a time window of 150-250 ms in the right occipital area, 200-250 ms in the bilateral ventral occipitotemporal areas, and 200-250 ms and 200-300 ms in the left and right anterior temporal areas, respectively. These areas have been reported to be related to processing of visual-form/orthography and lexico-semantics, and the enhanced activation supports the hypothesis. However, the absence of the priming effect in the areas related to phonological processing implies that automatic phonological priming effect depends on task requirements.

Neuroimaging study on brain asymmetries in situs inversus totalis.

Situs inversus totalis (SI) is a rare condition in which all visceral organs are arranged as mirror images of the usual pattern. The objective of this study was to determine whether SI individuals have reversed brain asymmetries. We performed a neuroimaging study on 3 SI subjects and 11 control individuals with normally arranged visceral organs. The language-dominant hemisphere was determined by magnetoencephalography. Left-hemispheric dominance was observed in 1 SI subject and all controls, whereas right-hemispheric dominance was observed in the remaining 2 SI subjects. Statistical analysis revealed that language dominance patterns in SI subjects were different from those in the controls, suggesting that the developmental mechanisms underlying visceral organ asymmetries are related to those underlying functional brain asymmetry. Anatomical brain asymmetries were determined by magnetic resonance imaging. SI subjects had the same planum temporale (PT) asymmetry pattern as the controls, but a reversed petalia asymmetry pattern. The inferior frontal gyrus (IFG) asymmetry pattern varied within both groups, indicating a relationship between the rightward IFG and right-hemispheric language dominance. These results suggest that the developmental mechanisms underlying visceral organ asymmetries are related to those underlying petalia asymmetry but not to those underlying PT and IFG asymmetries, and that brain asymmetries might develop via multiple region-dependent mechanisms.

Neural activations correlated with reading speed during reading novels.

Functional magnetic resonance imaging was used to measure neural activations in subjects instructed to silently read novels at ordinary and rapid speeds. Among the 19 subjects, 8 were experts in a rapid reading technique. Subjects pressed a button to turn pages during reading, and the interval between turning pages was recorded to evaluate the reading speed. For each subject, we evaluated activations in 14 areas and at 2 instructed reading speeds. Neural activations decreased with increasing reading speed in the left middle and posterior superior temporal area, left inferior frontal area, left precentral area, and the anterior temporal areas of both hemispheres, which have been reported to be active for linguistic processes, while neural activation increased with increasing reading speed in the right intraparietal sulcus, which is considered to reflect visuo-spatial processes. Despite the considerable reading speed differences, correlation analysis showed no significant difference in activation dependence on reading speed with respect to the subject groups and instructed reading speeds. The activation reduction with speed increase in language-related areas was opposite to the previous reports for low reading speeds. The present results suggest that subjects reduced linguistic processes with reading speed increase from ordinary to rapid speed.

Early neural activation for lexico-semantic access in the left anterior temporal area analyzed by an fMRI-assisted MEG multidipole method.

To determine the time and location of lexico-semantic access, we measured neural activations by magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) and estimated the neural sources by fMRI-assisted MEG multidipole analysis. Since the activations for phonological processing and lexico-semantic access were reported to overlap in many brain areas, we compared the activations in lexical and phonological decision tasks. The former task required visual form processing, phonological processing, and lexico-semantic access, while the latter task required only visual form and phonological processing, with similar phonological task demands for both tasks. The activation areas observed among 9 or 10 subjects out of 10 were the superior temporal and inferior parietal areas, anterior temporal area, and inferior frontal area of both hemispheres, and the left ventral occipitotemporal area. The activations showed a significant difference between the 2 tasks in the left anterior temporal area in all 50-ms time windows between 200-400 ms from the onset of visual stimulus presentation. Previous studies on semantic dementia and neuroimaging studies on normal subjects have shown that this area plays a key role in accessing semantic knowledge. The difference between the tasks appeared in common to all areas in the time windows of 100-150 ms and 400-450 ms, suggesting early differences in visual form processing and late differences in the decision process, respectively. The present results demonstrate that the activations for lexico-semantic access in the left anterior temporal area start in the time window of 200-250 ms, after early visual form processing.

Phonological influences on lexicosemantic processing of kanji words.

To investigate the phonological influences on the lexicosemantic process with a strong orthographic constraint, we used kanji (morphogram) homophone words and measured, using magnetoencephalography, the neural activities during the silent reading of prime-target pairs. The primes were phonologically the same as or different from the targets or pseudocharacters. The neural activities in the left posterior temporal and inferior parietal areas became weaker with phonological repetition. Furthermore, stronger activities for the different condition in the left anterior temporal area and for the same condition in the left inferior frontal cortex, respectively, suggest the roles of these areas of the brain in the semantic processing of words and in the selection of appropriate meanings. We conclude that phonological information affects the lexicosemantic process even with a strong orthographic constraint.

Lexical access and selection of contextually appropriate meaning for ambiguous words.

To clarify the neural mechanisms of lexical access and selection of contextually appropriate meanings for ambiguous words, we investigated the spatio-temporal characteristics of neural activities during silent reading and semantic judgment of lexically ambiguous or unambiguous target words that were preceded by semantically related or unrelated words by using magnetoencephalography. The left posterior superior temporal/inferior parietal area and the left anterior middle/inferior temporal area consistently showed a clear context effect, regardless of the ambiguity: the activities for related words were weaker than those for unrelated words. The activities in the left inferior frontal cortex, in contrast, were influenced by ambiguities. From approximately 200 to 300 ms, the activities in the left anterior inferior frontal cortex (aIFC) were stronger for ambiguous words than for unambiguous words, regardless of context. The stronger activities in the left aIFC, reflecting an increase in controlled semantic retrieval, indicate that multiple meanings for lexically ambiguous words are accessed irrespective of context. At approximately 400 ms, the left posterior inferior frontal cortex (pIFC) showed a clear context effect for unambiguous words but not for ambiguous ones. In addition, the activation in the left pIFC was stronger for related ambiguous words than for related unambiguous ones. These results suggest that in ambiguous words, not only contextually appropriate meanings but also two or more inappropriate meanings would be semantically integrated with a context. We conclude that the left IFC plays an important role in selecting an appropriate meaning from multiple alternatives after the integration of contextual information.

Late response evoked by cerebellar stimuli: effect of optokinetic stimulation.

We previously demonstrated that late electromyographic responses with a latency of 100 ms were evoked bilaterally in soleus muscles following transcranial magnetic stimulation over the left cerebellum. Efferent fibers from the left cerebellum modulate vestibulospinal tract influences on the extensor muscles of the left hindlimb. Here, we investigated whether the vestibulospinal tract mediates this late response. We activated the vestibulospinal tract by optokinetic stimulation. Our results show that the latency of the soleus electromyographic response is shortened by optokinetic stimulation, but the latency of the motor response evoked by the corticospinal tract is unchanged. These findings support our hypothesis that vestibulospinal tracts mediate late electromyographic responses, and allow the development of techniques to assess the human vestibulospinal system function.

Blockade of leukotriene B4 signaling pathway induces apoptosis and suppresses cell proliferation in colon cancer.

We investigated whether leukotriene B(4) (LTB(4)) and its signaling pathway play an important role in the progression of human colon cancer via a direct stimulation of cancer cell proliferation. Remarkable expression of LTB(4) receptor 1 (BLT1) in human colon cancer tissues was detected by immunohistochemistry, and Western blot analysis revealed the BLT1 expression in cultured human colon cancer cell lines, Caco2 and HT29. The 5-lipoxygenase inhibitor AA-861 and LTB(4)-receptor antagonist U75302 showed negative effects on survival and proliferation of both Caco2 and HT-29 cells. The inhibition of cell proliferation is due to the apoptosis because nuclear condensation and increased annexin V expression were observed in the cells treated with AA-861 and U75302. Knockdown of BLT1 by small interfering RNA caused the suppression of BLT1 protein, resulting in the inhibition of cancer cell proliferation. Blockade of BLT1 by the receptor antagonist significantly suppresses the LTB(4)-stimulated extracellular signal-regulated kinase (ERK) activation in colon cancer cells. These results indicate that the blockade of the LTB(4)-signaling pathway induces apoptosis via the inhibition of ERK activation in colon cancer cells. The LTB(4)-signaling pathway might be a new therapeutic target for colon cancer.